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Notes: Summary Background Psoriasis may have a severe impact on patients' quality of life (QOL) in several ways, an impact mediated by the mental or physical difficulties they have to deal with during the course of the disease and the various treatment regimens. In addition, psoriatic patients often suffer from experiences of stigmatization (EOS) related to the disease. Objectives This study was designed to test the hypotheses that psoriasis patients report higher levels of stigmatization than a comparison group, and that their EOS play a role in mediating the impact of the severity of psoriasis on their QOL. Methods One hundred patients with psoriasis (study group) and 100 patients with mixed skin problems (comparison group) were matched according to age, sex and education. All subjects answered questionnaires on EOS and QOL. A dermatologist diagnosed the diseases and measured severity scores. The Psoriasis Area and Severity Index score was used for psoriasis and a linear severity score for the comparison patients. The mediating effect of EOS was analysed using structural equation modelling (SEM). SEM is a multivariate statistical method used to examine the consistency of a theory relating one group of variables (termed a ‘latent construct’) to another: in the present study, the relationship between EOS and QOL. Results Psoriatic patients were found to report significantly higher levels of EOS related to the disease, compared with the comparison group. No significant differences were found regarding QOL or severity of disease. Clinical severity of psoriasis was found to correlate negatively with QOL in psoriasis patients. EOS were found to have a complete mediating effect for the severity of disease on the QOL in patients with psoriasis. This result was not found among the comparison group patients. Conclusions The results of this study indicate that psoriasis patients experience higher levels of stigmatization than do other dermatological patients, and that these EOS mediate the association between disease severity and patients' reported low levels of QOL. Treatment of psoriatic patients should consider these results and should include tools for psychosocial intervention.